ArticleEuropean journal of human genetics : EJHG2018
Distinct variants affecting differential splicing of TGFBR1 exon 5 cause either Loeys-Dietz syndrome or multiple self-healing squamous epithelioma.
Article in European journal of human genetics : EJHG, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 16 citations in OpenAlex.
- Decoding clinical diversity in monogenic TGFBR1 and TGFBR2 mutations: insights into the interplay of molecular mechanisms and hypomorphicity.Frontiers in cell and developmental biology · 2025Review
- Novel variant alters splicing ofFrontiers in genetics · 2024Article
- A novel pathogenic variant located just upstream of the C-terminal Ser423-X-Ser425 phosphorylation motif in SMAD3 causing Loeys-Dietz syndrome.Molecular genetics & genomic medicine · 2023Article
- Truncating variants in the penultimate exon of TGFBR1 escaping nonsense-mediated mRNA decay cause Loeys-Dietz syndrome.European journal of human genetics : EJHG · 2023Article
- The implications of alternative pre-mRNA splicing in cell signal transduction.Experimental & molecular medicine · 2023Review
- Association of gene polymorphisms in MYH11 and TGF-β signaling with the susceptibility and clinical outcomes of DeBakey type III aortic dissection.Mammalian genome : official journal of the International Mammalian Genome Society · 2022Article
- Germline Mutations for Kidney Volume in ADPKD.Kidney international reports · 2022Article
- Non-Melanoma Skin Cancers and Other Cutaneous Manifestations in Bone Marrow Failure Syndromes and Rare DNA Repair Disorders.Frontiers in oncology · 2022Review
- Expanding the phenotypic spectrum of Mendelian connective tissue disorders to include prominent kidney phenotypes.American journal of medical genetics. Part A · 2021Article
- Application of CRISPR-Cas9 gene editing for congenital heart disease.Clinical and experimental pediatrics · 2021Article
- Review
- Inhibition of transforming growth factor-β signaling in myeloid cells ameliorates aortic aneurysmal formation in Marfan syndrome.PloS one · 2020Article
- Unique Mechanism by WhichCirculation reports · 2019Review
- Activation of TGF-β signaling in an aortic aneurysm in a patient with Loeys-Dietz syndrome caused by a novel loss-of-function variant ofHuman genome variation · 2019Article
- TGF-β Signaling-Related Genes and Thoracic Aortic Aneurysms and Dissections.International journal of molecular sciences · 2018Review
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Authors and funding
17 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Variants in TGFBR1 have been reported to induce two completely distinct diseases, namely Loeys-Dietz syndrome (LDS) and multiple self-healing squamous epithelioma (MSSE). However, detailed mechanisms underlying this effect remain unknown. We report a Japanese familial case of LDS with a novel splice donor site variant in TGFBR1 gene (c.973 + 1 G > A; NG_007461.1). The intronic variant was predicted to mediate in-frame exon 5 skipping within the serine/threonine kinase (STK) domain, which may also be mediated by a similar TGFBR1 variant of a splice acceptor site in intron 4 (c.806-2 A > C), identified in a British familial case of MSSE. Therefore, ex vivo splicing and functional assays were performed in mammalian cells to evaluate the effect of these sequence variants. The MSSE variant activated a cryptic acceptor site at 76 bp downstream of the 3' natural splice acceptor site, which produced an out-of-frame transcript (r.807_882del, p.Asn270Thrfs*8). In contrast, the LDS variant generated two types of in-frame transcription products, r.[806_973del, 965_973 del], and produced two functionally inactivated proteins, p.[Asp269_Gln324del, Thr323_Gly325del], as a result of exon 5 skipping and the activation of a cryptic donor splice site at 9 bp upstream of the 5' natural splice donor site, respectively. Our results support the previously proposed but not yet approved mechanism that dominant-negative and truncating variants in STK domain induce LDS and MSSE, respectively.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.